Title
Identification of neutral biochemical network models from time series data.
Abstract
The major difficulty in modeling biological systems from multivariate time series is the identification of parameter sets that endow a model with dynamical behaviors sufficiently similar to the experimental data. Directly related to this parameter estimation issue is the task of identifying the structure and regulation of ill-characterized systems. Both tasks are simplified if the mathematical model is canonical, i.e., if it is constructed according to strict guidelines.In this report, we propose a method for the identification of admissible parameter sets of canonical S-systems from biological time series. The method is based on a Monte Carlo process that is combined with an improved version of our previous parameter optimization algorithm. The method maps the parameter space into the network space, which characterizes the connectivity among components, by creating an ensemble of decoupled S-system models that imitate the dynamical behavior of the time series with sufficient accuracy. The concept of sloppiness is revisited in the context of these S-system models with an exploration not only of different parameter sets that produce similar dynamical behaviors but also different network topologies that yield dynamical similarity.The proposed parameter estimation methodology was applied to actual time series data from the glycolytic pathway of the bacterium Lactococcus lactis and led to ensembles of models with different network topologies. In parallel, the parameter optimization algorithm was applied to the same dynamical data upon imposing a pre-specified network topology derived from prior biological knowledge, and the results from both strategies were compared. The results suggest that the proposed method may serve as a powerful exploration tool for testing hypotheses and the design of new experiments.
Year
DOI
Venue
2009
10.1186/1752-0509-3-47
BMC systems biology
Keywords
Field
DocType
mathematical model,time series data,dynamic data,glycolysis,biological systems,time series,data analysis,parameter estimation,kinetics,monte carlo,parameter space,algorithms,monte carlo method,mathematical models,methodology,system modeling,network topology
Time series,Experimental data,Identifiability,Biological network,Computer science,Robustness (computer science),Bioinformatics,Estimation theory,Mathematical model,Network model
Journal
Volume
Issue
ISSN
3
1
1752-0509
Citations 
PageRank 
References 
11
1.11
17
Authors
5
Name
Order
Citations
PageRank
Marco Vilela1865.18
Susana Vinga253537.72
Marco A Grivet Mattoso Maia3141.63
Eberhard O. Voit433029.03
Jonas S Almeida573142.25